Bladder cancer is the second most common genitourinary tumor, and more than 90% of these tumors are urothelial carcinomas. Almost 25% of patients with newly diagnosed bladder cancer have MIBC, with the vast majority of these tumors being of high histological grade. Moreover, nearly 50% of patients with MIBC already have occult distant metastases at the time of diagnosis.
Although radical cystectomy is the standard treatment for MIBC, about 50% of these patients develop metastases within 2 years, and the 5 year survival rate after surgery alone is approximately 50%. Systemic cisplatin-based combination chemotherapy is the first-line treatment modality for patients with metastatic bladder cancer. However, despite the initial high response rates of 40 to 70% reported in patients with advanced disease, chemotherapy is usually not curative and the overall 5 year survival is only 5 to 15%. Performance status and the presence of visceral metastases are well-established prognostic markers demonstrated to predict a poor prognosis in patients treated with cisplatin-based chemotherapy. However, while these clinicopathological markers are useful as survival indicators, they are inadequate to predict either the response rate or the survival rate in an individual patient. Accordingly, there is growing interest in the role played by genes in the chemotherapeutic response of patients with MIBC and the predictive power of this relationship in an individual patient.
Thus far, information that would allow the response to chemotherapy to be predicted in an individual patient is lacking in the case of MIBC as well as many other cancers. Consequently, some patients suffer the adverse side effects of these highly toxic drugs without the benefit of their intended action. Perhaps even more important is that, as their physical condition worsens, some of these unnecessarily treated patients may be deprived of additional therapy.
In our previous study, a gene expression profile analysis was carried out with the aim of identifying a genetic signature for progression in MIBC patients. Among the 1,320 genes thus identified by microarray data analysis, four genes (IL1B, S100A8, S100A9, and EGFR) were determined to be important in predicting disease progression. In the present study, we asked whether this four-gene signature could be used to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC.